Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
Departamento de Ciencias Médicas Básicas (Fisiología) and Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna, Tenerife, Spain.
Elife. 2021 Apr 1;10:e67267. doi: 10.7554/eLife.67267.
Insulin-like growth factor-1 (IGF-1) plays a key role in synaptic plasticity, spatial learning, and anxiety-like behavioral processes. While IGF-1 regulates neuronal firing and synaptic transmission in many areas of the central nervous system, its signaling and consequences on excitability, synaptic plasticity, and animal behavior dependent on the prefrontal cortex remain unexplored. Here, we show that IGF-1 induces a long-lasting depression of the medium and slow post-spike afterhyperpolarization (mAHP and sAHP), increasing the excitability of layer 5 pyramidal neurons of the rat infralimbic cortex. Besides, IGF-1 mediates a presynaptic long-term depression of both inhibitory and excitatory synaptic transmission in these neurons. The net effect of this IGF-1-mediated synaptic plasticity is a long-term potentiation of the postsynaptic potentials. Moreover, we demonstrate that IGF-1 favors the fear extinction memory. These results show novel functional consequences of IGF-1 signaling, revealing IGF-1 as a key element in the control of the fear extinction memory.
胰岛素样生长因子-1（IGF-1）在突触可塑性、空间学习和焦虑样行为过程中发挥着关键作用。虽然 IGF-1 调节中枢神经系统许多区域的神经元放电和突触传递，但它对兴奋性、突触可塑性和依赖前额叶皮层的动物行为的信号转导和后果仍未得到探索。在这里，我们表明 IGF-1 诱导大鼠扣带皮层 5 层锥体神经元中中速和慢速后超极化（mAHP 和 sAHP）的长时抑制，从而增加神经元的兴奋性。此外，IGF-1 介导这些神经元中抑制性和兴奋性突触传递的长时突触前抑制。这种 IGF-1 介导的突触可塑性的净效应是突触后电位的长时增强。此外，我们证明 IGF-1 有利于恐惧消退记忆。这些结果显示了 IGF-1 信号转导的新功能后果，揭示了 IGF-1 是控制恐惧消退记忆的关键因素。
